Insulin is a polypeptide hormone secreted by β-cells of the pancreas. Insulin consists of two polypeptide chains designated the A and B chains which are linked together by two inter-chain disulphide bridges. In human, porcine and bovine insulin, the A and B chains contains 21 and 30 amino acid residues, respectively. However, from species to species, there are variations among the amino acid residues present in the different positions in the two chains. The widespread use of genetic engineering has made it possible to prepare analogues of natural occurring insulins by exchanging one of more of the amino acid residues.
Insulin is used for the treatment of diabetes and diseases connected therewith or resulting from it. Insulin is essential in maintaining normal metabolic regulation. Usually, insulin is administered by injections. Unfortunately, many diabetics are unwilling to undertake intensive therapy due to the discomfort associated with the many injections required to maintain close control of glucose levels. Upon oral administration, insulin is rapidly degraded in the gastro intestinal tract and is not absorbed into the blood stream. Therefore, alternate routes for administering insulin, such as oral, rectal, transdermal, and nasal routes have been investigated. Thus far, however, these routes of administration have not resulted in sufficiently effective insulin absorption.
For decades, both long-acting insulin preparations and fast acting insulin preparations have been available and many patients take 2-4 injections per day. In the last decades, it has turned out that it is extremely important for a diabetic patient to maintain close control of the blood glucose level.
International patent application number having publication number WO 2007/096431 which was published on 30 Aug. 2007 (Novo Nordisk A/S) describes insulins having a complex side chain with no alkylene glycol moieties. International patent application having publication number WO 2006/-082205 (Novo Nordisk A/S) describes insulins having a complex side chain connected to an amino acid in the B chain. According to claim 1, U.S. Pat. No. 6,444,641 B1 relates to a fatty acid-acylated insulin analog comprising an insulin analog to which a fatty acyl chain is joined by an amide bond, wherein said fatty insulin analog has an isoelectric point that is higher than the isoelectric point of insulin. According to claim 1, WO 2006/082205 (Novo Nordisk NS) relates to insulin derivatives having a side chain attached either to the α-amino group of the N-terminal amino acid residue of B chain or to an ε-amino group of a Lys residue present in the B chain of the parent insulin molecule. Pharm. Res. 21 (2004), 1498-1504, deals with the mechanism of protraction of insulin detemir.